THE JOURNAL OF INFECTIOUS DISEASES • VOL. 133, NO.3' © 1976 by the University of Chicago. All rights reserved.
MARCH 1976
Equal Susceptibility of Males and Females on Santa Cruz Island to the Carrier State of Hepatitis B Surface Antigen Scott Mazzur
~nd
From the American National Red Cross Blood Research Laboratory, Bethesda, Maryland; and the Medical Department, Santa Cruz Island, British Solomon Islands Protectorate
Norman Jones
Previous workers have described a preponderance of male carriers of hepatitis B surface antigen (HB s Ag) in almost all populations studied. Goodman et al. [1] studied the population of an institution for the mentally retarded. They found that karyotypically normal female patients had a much lower incidence of HB s Ag than did males, although the prevalence of carriers among G-trisomic individuals of both sexes was high. These workers attributed the difference in frequency of HB s Ag to a sex-dependent difference in susceptibility to the chronic carrier state. Several other studies of asymptomatic populations have shown a similar preponderance of male carriers
preponderance of male carriers. Although these authors mentioned the possibility that the activities and increased number of exposures of males may make them more likely than females to become infected, they suggested that the increased frequency of HB s Ag carriage in males is probably due to differences in susceptibility related to sex-dependent differences in immunoresponsiveness. Szmuness et al. [7, 8] observed a preponderance of male carriers among children, but not among adults, in two populations, one in the Republic of Senegal and the other in closed institutions for the mentally retarded in the United States. We have studied a population in the British Solomon Island Protectorate that is known to have a higher frequency of male carriers than of female carriers [9]. We have tested for both HB s Ag and antibody to HB s Ag (anti-HB s )' The distribution of antigen and antibody in males has been compared with that in females in an effort to distinguish between two hypotheses concerning the higher frequency of HBs Ag among males. The first hypothesis is that the high frequency of carriage among males is due to an increased susceptibility to the carrier state. In this case the frequency of carriage among males would be higher than that among females, and the ratio of the frequency of antigen to that of antibody would be lower in males than in females, since more of the males exposed would become carriers. The
[2-5].
Blumberg et al. [6], summarizing data on 13 populations of asymptomatic individuals in the South Pacific and Asia, demonstrated a consistent
Received for publication May 27, 1975, and in revised form November 11, 1975. This work was supported in part by grant no. GM 20,222 from the National Institute of General Medical Sciences. We thank Mr. James Tedder, Dr. James-Macgregor, Obeta Tioti, Basil Silibasi, and Donation Bulu, whose assistance made this study possible. Please address requests for reprints to Dr. Scott Mazzur, American National Red Cross Blood Research Laboratory, 9312 Old Georgetown Road, Bethesda, Maryland 20014.
331
Downloaded from http://jid.oxfordjournals.org/ at University of Sussex on August 29, 2015
Various studies have shown that hepatitis B surface antigen is detected more frequently in the blood of asymptomatic males than in that of asymptomatic females. The reason for this difference might be that males are more frequently infected than females or that males more frequently· become asymptomatic carriers when they are infected. The sex distribution of hepatitis B surface antigen and antibody, as measured by reversed passive_.hemagglutination and passive hemagglutination, was determined in a Melanesian population. The frequency of the antigen was higher among males, but the ratio of antigen to antibody was the same in both sexes. This finding indicated that the higher frequency in males was due to a higher rate of infection rather than to a greater susceptibility of the males to the chronic carrier state.
A1azzur and Jones
332
alternative hypothesis is that, when infected, males and females are equally susceptible to the carrier state, and the preponderance of male carriers is due to a higher rate of infection among males. In this case the ratio of antigen to antibody in males would be the same as that in females. Materials and Methods
Results
The ratio of male antigen carriers to female antigen carriers in this population was 1.6: 1. All carriers were apparently healthy when given a routine physical examination. The antigen was detected in 50 of the 403 males tested (12 % ) and in 31 of the 368 females tested (8 % ). The incidence of antibody was also higher among males than among females (25 % vs. 17%). A '1.2 analysis of these data indicated that, although there were more male than female carriers of HB s Ag, the distribution in males was not significantly different from that in females ('1. 2 == 2.8358). However, the prevalence of antibody in males was significantly higher than that in females ('1. 2 == 8.2853; P < 0.01). The ratio of antigen to antibody in males and females of all ages was exactly the same (1: 2). This ratio did vary according to age group, but the trend was similar in both sexes. These differences were probably
Discussion
Santa Cruz is an island in the eastern district of the British Solomon Islands Protectorate. The population of Graciosa Bay lives in leaf houses along the shores of the bay. The people. are Melanesians and are well nourished. Their main health problems are malaria, filariasis, and tuberculosis and other respiratory infections. The ratio of male to female HB s Ag carriers in this population is 1.6: 1. This finding is similar to those of several other investigators studying different populations. However, the data presented in this paper indicate that the ratio of HB s Ag to antiHB s is the same in males and females. We assume on the basis of evidence in the literature that a person infected with hepatitis B virus may (1) become a carrier of· HB s Ag and develop antiHB s ; (2) become a carrier of HB s Ag but fail to develop anti-HB s ; or (3) fail to become a carrier of HB s Ag but develop anti-HB s . It is possible that some persons who have been infected with hepatitis B virus may have antibody or antigen at levels undetectable by the methods employed. However, it is assumed that such a group would be made up of· an equal number of males and females. If these assumptions are made, our data show that, when infected with hepatitis B virus, males and females are equally susceptible to the carrier state of HB s Ag. The combined frequency of HB s Ag and anti-HB s in females is 23 %, compared with 38% in males. This difference may be due to a higher rate of exposure in males or to a greater susceptibility to infection. On Santa Cruz the male children play together in groups from the time when they first begin to walk, while the female children constantly stay beside their mothers and help with domestic duties. Sometime between the age of six and 12 years, the young boys begin to move away from their parents' house and finally live entirely in communal single men's houses until marriage [11]. Thus the males are intimately exposed to many more individuals than the females. This exposure may include any of the factors involved in living and playing together, e.g., shared utensils and sleeping mats, close proximity during sleeping hours, or com-
Downloaded from http://jid.oxfordjournals.org/ at University of Sussex on August 29, 2015
We tested the entire population of Graciosa Bay, Santa Cruz Island. This population included 771 individuals ranging in age from birth to over 65 years. Blood was collected in plain capillary tubes by pricking of the finger or the heel. The serum was separated from the clot and tested by reversed passive HA for HB s Ag and by passive HA for anti-HB s • The Abbott Auscell® system (Abbott Laboratories, North Chicago, Ill.) was utilized for detection of antigen. In this test HBi) Ag is detected by the agglutination of human cells coated with purified anti-HB s [l 0]. A similar system for the detection of antibody through use of cells coated with HB s Ag was kindly provided by Dr. Lacy Overby of Abbott Laboratories. All sera were screened in both tests, and positive reactions were confirmed by specific neutralization with either the antigen or the antibody (whichever was appropriate) .
due to age-related host response and to culturally conditioned exposure rates.
333
Susceptibility to Carrier State of HB 8 Ag
H
References
1. Goodman, M., Wainwright, R L., Weir, H. F., Gall, J. C., Jr. A sex difference in the carrier state of Australia antigen. Pediatrics 48:907-913, 1971. 2. Szmuness, W., Prince, A. M., Brotman, B., Hirsch, R. L. Hepatitis B antigen and antibody in blood donors: an epidemiologic study. J. Infect. Dis. 127: 17-25, 1973.
3. Banke, 0., Dybkjaer, E., Nordenfelt, E., Reinicke, V. Australia antigen and antibody in 10,000 Danish blood donors. Lancet 1:860-861, 1971. 4. Szmuness, W., Hirsch, R. L., Prince, A. M., Levine, R. W., Harley, E. J., Ikram, H. Hepatitis B surface antigen in blood donors: further observations. J. Infect. Dis. 131:111-118, 1975. 5. Grossman, R A., Benenson, M. W., Scott, R. M.; Snitbhan, R., Top, F. H., Jr., Pantuwatana, S. An epidemiological study of hepatitis B virus in Bangkok, Thailand. Am. J. Epidemiol. 101: 144-159, 1975. 6. Blumberg, B. S., Sutnick, A. L., London, W. T., Melartin, L. Sex distribution of Australia antigen. Arch. Intern. Med. 130:227-231, 1972. 7. Szmuness, W., Prince, A. M., Diebolt, G., Leblanc, L., Baylet, R, Masseyeff, R., Linhard, J. The epidemiology of hepatitis B infections in Africa: results of a pilot survey in the Republic of Senegal. Am. J. Epidemiol. 98: 104-110, 1973. 8. Szmuness, W., Pick, R., Prince, A. M. Serum hepatitis virus specific antigen (SH): a preliminary report of epidemiologic studies in an institution for the mentally retarded. Am. J. Epidemiol. 92: 51-61, 1970. 9. Mazzur, S., Watson, T. M. Excess males among siblings of Australia antigen carriers. Nature (Lond.) 250:60-61, 1974. 10. Juji, T., Yokochi, T. Hemagglutination technique with erythrocyte coated with specific antibody for detection of Australia antigen. Jpn. J. Exp. Med. 39:615-620, 1973. 11. Davenport, W. Social structure of Santa Cruz Island. In W. H. Goodenough [ed.]. Explorations in cultural anthropology. McGraw-Hill, New York, 1964, p. 57-93. 12. Davenport, W. Sexual patterns and their regulation in a society of the South West Pacific. In F. A. Beach [ed.]. Sex and behavior. John Wiley and Sons, New York, 1965, p. 164-207.
Downloaded from http://jid.oxfordjournals.org/ at University of Sussex on August 29, 2015
mon exposure to bedbugs. In addition, homosexuality is an accepted practice in this culture [12]. Thus in this environment boys are exposed to a greater number of individuals and therefore to more HB s Ag carriers. Grossman et al. have made similar observations in Thailand [5]. The prevalence of HB s Ag was higher in males than in females, both overall and, in particular, in individuals 10-29 years old. The prevalence of anti-HB s was also higher in males up to age 60. The females had a high prevalence of HB s Ag in early life and a high prevalence of both HB s Ag and anti-HB in the later adult years. The authors attribute these differences in antigen and antibody distribution among males and females to differences in childrearing patterns that lead to greater exposure of male children [5]. Thus a culturally determined increase in exposure of males, which would be expected to result in higher rates of infection, provides an explanation for the higher frequency of male carriers of HBs Ag in these populations.
MARCH 1976
Equal Susceptibility of Males and Females on Santa Cruz Island to the Carrier State of Hepatitis B Surface Antigen Scott Mazzur
~nd
From the American National Red Cross Blood Research Laboratory, Bethesda, Maryland; and the Medical Department, Santa Cruz Island, British Solomon Islands Protectorate
Norman Jones
Previous workers have described a preponderance of male carriers of hepatitis B surface antigen (HB s Ag) in almost all populations studied. Goodman et al. [1] studied the population of an institution for the mentally retarded. They found that karyotypically normal female patients had a much lower incidence of HB s Ag than did males, although the prevalence of carriers among G-trisomic individuals of both sexes was high. These workers attributed the difference in frequency of HB s Ag to a sex-dependent difference in susceptibility to the chronic carrier state. Several other studies of asymptomatic populations have shown a similar preponderance of male carriers
preponderance of male carriers. Although these authors mentioned the possibility that the activities and increased number of exposures of males may make them more likely than females to become infected, they suggested that the increased frequency of HB s Ag carriage in males is probably due to differences in susceptibility related to sex-dependent differences in immunoresponsiveness. Szmuness et al. [7, 8] observed a preponderance of male carriers among children, but not among adults, in two populations, one in the Republic of Senegal and the other in closed institutions for the mentally retarded in the United States. We have studied a population in the British Solomon Island Protectorate that is known to have a higher frequency of male carriers than of female carriers [9]. We have tested for both HB s Ag and antibody to HB s Ag (anti-HB s )' The distribution of antigen and antibody in males has been compared with that in females in an effort to distinguish between two hypotheses concerning the higher frequency of HBs Ag among males. The first hypothesis is that the high frequency of carriage among males is due to an increased susceptibility to the carrier state. In this case the frequency of carriage among males would be higher than that among females, and the ratio of the frequency of antigen to that of antibody would be lower in males than in females, since more of the males exposed would become carriers. The
[2-5].
Blumberg et al. [6], summarizing data on 13 populations of asymptomatic individuals in the South Pacific and Asia, demonstrated a consistent
Received for publication May 27, 1975, and in revised form November 11, 1975. This work was supported in part by grant no. GM 20,222 from the National Institute of General Medical Sciences. We thank Mr. James Tedder, Dr. James-Macgregor, Obeta Tioti, Basil Silibasi, and Donation Bulu, whose assistance made this study possible. Please address requests for reprints to Dr. Scott Mazzur, American National Red Cross Blood Research Laboratory, 9312 Old Georgetown Road, Bethesda, Maryland 20014.
331
Downloaded from http://jid.oxfordjournals.org/ at University of Sussex on August 29, 2015
Various studies have shown that hepatitis B surface antigen is detected more frequently in the blood of asymptomatic males than in that of asymptomatic females. The reason for this difference might be that males are more frequently infected than females or that males more frequently· become asymptomatic carriers when they are infected. The sex distribution of hepatitis B surface antigen and antibody, as measured by reversed passive_.hemagglutination and passive hemagglutination, was determined in a Melanesian population. The frequency of the antigen was higher among males, but the ratio of antigen to antibody was the same in both sexes. This finding indicated that the higher frequency in males was due to a higher rate of infection rather than to a greater susceptibility of the males to the chronic carrier state.
A1azzur and Jones
332
alternative hypothesis is that, when infected, males and females are equally susceptible to the carrier state, and the preponderance of male carriers is due to a higher rate of infection among males. In this case the ratio of antigen to antibody in males would be the same as that in females. Materials and Methods
Results
The ratio of male antigen carriers to female antigen carriers in this population was 1.6: 1. All carriers were apparently healthy when given a routine physical examination. The antigen was detected in 50 of the 403 males tested (12 % ) and in 31 of the 368 females tested (8 % ). The incidence of antibody was also higher among males than among females (25 % vs. 17%). A '1.2 analysis of these data indicated that, although there were more male than female carriers of HB s Ag, the distribution in males was not significantly different from that in females ('1. 2 == 2.8358). However, the prevalence of antibody in males was significantly higher than that in females ('1. 2 == 8.2853; P < 0.01). The ratio of antigen to antibody in males and females of all ages was exactly the same (1: 2). This ratio did vary according to age group, but the trend was similar in both sexes. These differences were probably
Discussion
Santa Cruz is an island in the eastern district of the British Solomon Islands Protectorate. The population of Graciosa Bay lives in leaf houses along the shores of the bay. The people. are Melanesians and are well nourished. Their main health problems are malaria, filariasis, and tuberculosis and other respiratory infections. The ratio of male to female HB s Ag carriers in this population is 1.6: 1. This finding is similar to those of several other investigators studying different populations. However, the data presented in this paper indicate that the ratio of HB s Ag to antiHB s is the same in males and females. We assume on the basis of evidence in the literature that a person infected with hepatitis B virus may (1) become a carrier of· HB s Ag and develop antiHB s ; (2) become a carrier of HB s Ag but fail to develop anti-HB s ; or (3) fail to become a carrier of HB s Ag but develop anti-HB s . It is possible that some persons who have been infected with hepatitis B virus may have antibody or antigen at levels undetectable by the methods employed. However, it is assumed that such a group would be made up of· an equal number of males and females. If these assumptions are made, our data show that, when infected with hepatitis B virus, males and females are equally susceptible to the carrier state of HB s Ag. The combined frequency of HB s Ag and anti-HB s in females is 23 %, compared with 38% in males. This difference may be due to a higher rate of exposure in males or to a greater susceptibility to infection. On Santa Cruz the male children play together in groups from the time when they first begin to walk, while the female children constantly stay beside their mothers and help with domestic duties. Sometime between the age of six and 12 years, the young boys begin to move away from their parents' house and finally live entirely in communal single men's houses until marriage [11]. Thus the males are intimately exposed to many more individuals than the females. This exposure may include any of the factors involved in living and playing together, e.g., shared utensils and sleeping mats, close proximity during sleeping hours, or com-
Downloaded from http://jid.oxfordjournals.org/ at University of Sussex on August 29, 2015
We tested the entire population of Graciosa Bay, Santa Cruz Island. This population included 771 individuals ranging in age from birth to over 65 years. Blood was collected in plain capillary tubes by pricking of the finger or the heel. The serum was separated from the clot and tested by reversed passive HA for HB s Ag and by passive HA for anti-HB s • The Abbott Auscell® system (Abbott Laboratories, North Chicago, Ill.) was utilized for detection of antigen. In this test HBi) Ag is detected by the agglutination of human cells coated with purified anti-HB s [l 0]. A similar system for the detection of antibody through use of cells coated with HB s Ag was kindly provided by Dr. Lacy Overby of Abbott Laboratories. All sera were screened in both tests, and positive reactions were confirmed by specific neutralization with either the antigen or the antibody (whichever was appropriate) .
due to age-related host response and to culturally conditioned exposure rates.
333
Susceptibility to Carrier State of HB 8 Ag
H
References
1. Goodman, M., Wainwright, R L., Weir, H. F., Gall, J. C., Jr. A sex difference in the carrier state of Australia antigen. Pediatrics 48:907-913, 1971. 2. Szmuness, W., Prince, A. M., Brotman, B., Hirsch, R. L. Hepatitis B antigen and antibody in blood donors: an epidemiologic study. J. Infect. Dis. 127: 17-25, 1973.
3. Banke, 0., Dybkjaer, E., Nordenfelt, E., Reinicke, V. Australia antigen and antibody in 10,000 Danish blood donors. Lancet 1:860-861, 1971. 4. Szmuness, W., Hirsch, R. L., Prince, A. M., Levine, R. W., Harley, E. J., Ikram, H. Hepatitis B surface antigen in blood donors: further observations. J. Infect. Dis. 131:111-118, 1975. 5. Grossman, R A., Benenson, M. W., Scott, R. M.; Snitbhan, R., Top, F. H., Jr., Pantuwatana, S. An epidemiological study of hepatitis B virus in Bangkok, Thailand. Am. J. Epidemiol. 101: 144-159, 1975. 6. Blumberg, B. S., Sutnick, A. L., London, W. T., Melartin, L. Sex distribution of Australia antigen. Arch. Intern. Med. 130:227-231, 1972. 7. Szmuness, W., Prince, A. M., Diebolt, G., Leblanc, L., Baylet, R, Masseyeff, R., Linhard, J. The epidemiology of hepatitis B infections in Africa: results of a pilot survey in the Republic of Senegal. Am. J. Epidemiol. 98: 104-110, 1973. 8. Szmuness, W., Pick, R., Prince, A. M. Serum hepatitis virus specific antigen (SH): a preliminary report of epidemiologic studies in an institution for the mentally retarded. Am. J. Epidemiol. 92: 51-61, 1970. 9. Mazzur, S., Watson, T. M. Excess males among siblings of Australia antigen carriers. Nature (Lond.) 250:60-61, 1974. 10. Juji, T., Yokochi, T. Hemagglutination technique with erythrocyte coated with specific antibody for detection of Australia antigen. Jpn. J. Exp. Med. 39:615-620, 1973. 11. Davenport, W. Social structure of Santa Cruz Island. In W. H. Goodenough [ed.]. Explorations in cultural anthropology. McGraw-Hill, New York, 1964, p. 57-93. 12. Davenport, W. Sexual patterns and their regulation in a society of the South West Pacific. In F. A. Beach [ed.]. Sex and behavior. John Wiley and Sons, New York, 1965, p. 164-207.
Downloaded from http://jid.oxfordjournals.org/ at University of Sussex on August 29, 2015
mon exposure to bedbugs. In addition, homosexuality is an accepted practice in this culture [12]. Thus in this environment boys are exposed to a greater number of individuals and therefore to more HB s Ag carriers. Grossman et al. have made similar observations in Thailand [5]. The prevalence of HB s Ag was higher in males than in females, both overall and, in particular, in individuals 10-29 years old. The prevalence of anti-HB s was also higher in males up to age 60. The females had a high prevalence of HB s Ag in early life and a high prevalence of both HB s Ag and anti-HB in the later adult years. The authors attribute these differences in antigen and antibody distribution among males and females to differences in childrearing patterns that lead to greater exposure of male children [5]. Thus a culturally determined increase in exposure of males, which would be expected to result in higher rates of infection, provides an explanation for the higher frequency of male carriers of HBs Ag in these populations.
